Comparison of Degree of Penetration of β-Blocker Ophthalmic Solution With and Without Preservative Into Rabbit Aqueous Humor

Abstract

Introduction: : M. Fukuda¹, H. Sasaki¹, K. Kitagawa¹, A. Kawai¹, Y. Seki¹, M. Yoshikawa²Ophthalmology, Kanazawa Medical University¹, Mayo Corporation²

Purpose: : Studies have shown that benzalkonium chloride (BAK), a preservative used in antiglaucoma medications, can increase the corneal penetration of the solution by acting as a penetration enhancer. The purpose of this study was to compare the penetration of a preservative-free β blocker ophthalmic solution to that of the same solution with 0.005% to 0.02% BAK into the aqueous humor of rabbits.

Methods: : Timoptol ophthalmic solution (0.5%) with 0%, 0.005%, and 0.02% BAK or 2% carteolol hydrochloride ophthalmic solution with 0%, 0.005%, and 0.02%BAK was dropped into the cul-de-sac of rabbit eyes. The changes in the electrical corneal resistance (CR) were measured before and 2 min after the BAK, and the relative CR (CR after/CR before) was calculated. Slit-lamp biomicroscopy of fluorescein stained corneas was used to confirm and grade the degree of corneal injury. The concentration of the solutions in the aqueous was measured at 60 min by high performance liquid chromatography (HPLC).

Results: : The relative CRs in eyes with topical 0.5% timoptol solution with 0, 0.005 and 0.02% BAK were 108.3±5.8%, 98.2 ± 12.3%, and 66.9±7.75%, respectively, at 2 min. The timoptol concentration in the aqueous humor was significantly higher after 0.005% BAK (5.62±2.9 µg/ml) and at 0.02% BAK (3.84±1.2 µg/ml; P<0.05) than after 0% BAK (3.65±1.33 µg/ml). The relative CR in eyes with topical 2% carteolol hydrochloride solution with 0 and 0.02% BAK were 98.9%, and 76.4% respectively, at 2min. The carteolol concentration in the aqueous humor was significantly higher after 0.02% BAK (1.8±0.4 µg/ml) than at 0% BAK (0.7±0.4 µg/ml; P<0.001). Fluorecein staining of the corneal epithelium was observed only in eyes with topical ophthalmic solution with 0.02% BAK at 2 min.

Conclusions: : These data indicate that BAK affect the corneal penetration of β-blocker ophthalmic solution into the rabbit aqueous humor.

Clinical Trial: : www.ctri.in H. Sasaki K. Kitagawa A.Kawi Y. Seki M.Yoshikawa

Keywords: aqueous • cornea: epithelium • drug toxicity/drug effects